scholarly journals Common Denominators in the Immunobiology of IgG4 Autoimmune Diseases: What Do Glomerulonephritis, Pemphigus Vulgaris, Myasthenia Gravis, Thrombotic Thrombocytopenic Purpura and Autoimmune Encephalitis Have in Common?

2021 ◽  
Vol 11 ◽  
Author(s):  
Inga Koneczny ◽  
Vuslat Yilmaz ◽  
Konstantinos Lazaridis ◽  
John Tzartos ◽  
Tobias L. Lenz ◽  
...  
Keyword(s):  
T Cells ◽  
Nervous System ◽  
Autoimmune Diseases ◽  
Myasthenia Gravis ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Autoimmune Encephalitis ◽  
Pemphigus Vulgaris ◽  
Class Ii ◽  
Hla Class Ii ◽  
Thrombocytopenic Purpura

IgG4 autoimmune diseases (IgG4-AID) are an emerging group of autoimmune diseases that are caused by pathogenic autoantibodies of the IgG4 subclass. It has only recently been appreciated, that members of this group share relevant immunobiological and therapeutic aspects even though different antigens, tissues and organs are affected: glomerulonephritis (kidney), pemphigus vulgaris (skin), thrombotic thrombocytopenic purpura (hematologic system) muscle-specific kinase (MuSK) in myasthenia gravis (peripheral nervous system) and autoimmune encephalitis (central nervous system) to give some examples. In all these diseases, patients’ IgG4 subclass autoantibodies block protein-protein interactions instead of causing complement mediated tissue injury, patients respond favorably to rituximab and share a genetic predisposition: at least five HLA class II genes have been reported in individual studies to be associated with several different IgG4-AID. This suggests a role for the HLA class II region and specifically the DRβ1 chain for aberrant priming of autoreactive T-cells toward a chronic immune response skewed toward the production of IgG4 subclass autoantibodies. The aim of this review is to provide an update on findings arguing for a common pathogenic mechanism in IgG4-AID in general and to provide hypotheses about the role of distinct HLA haplotypes, T-cells and cytokines in IgG4-AID.

scholarly journals Tristetraprolin/ZFP36 Regulates the Turnover of Autoimmune-Associated HLA-DQ mRNAs

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1570 ◽  
Author(s):  
Laura Pisapia ◽  
Russell S. Hamilton ◽  
Federica Farina ◽  
Vito D’Agostino ◽  
Pasquale Barba ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Diseases ◽  
Zinc Finger Protein ◽  
Class Ii ◽  
Hla Class Ii ◽  
Autoimmune Response ◽  
Risk Genes ◽  
Hla Dq ◽  
Rnp Complex ◽  
Hla Dqa1

HLA class II genes encode highly polymorphic heterodimeric proteins functioning to present antigens to T cells and stimulate a specific immune response. Many HLA genes are strongly associated with autoimmune diseases as they stimulate self-antigen specific CD4+ T cells driving pathogenic responses against host tissues or organs. High expression of HLA class II risk genes is associated with autoimmune diseases, influencing the strength of the CD4+ T-mediated autoimmune response. The expression of HLA class II genes is regulated at both transcriptional and post-transcriptional levels. Protein components of the RNP complex binding the 3′UTR and affecting mRNA processing have previously been identified. Following on from this, the regulation of HLA-DQ2.5 risk genes, the main susceptibility genetic factor for celiac disease (CD), was investigated. The DQ2.5 molecule, encoded by HLA-DQA1*05 and HLA-DQB1*02 alleles, presents the antigenic gluten peptides to CD4+ T lymphocytes, activating the autoimmune response. The zinc-finger protein Tristetraprolin (TTP) or ZFP36 was identified to be a component of the RNP complex and has been described as a factor modulating mRNA stability. The 3′UTR of CD-associated HLA-DQA1*05 and HLA-DQB1*02 mRNAs do not contain canonical TTP binding consensus sequences, therefore an in silico approach focusing on mRNA secondary structure accessibility and stability was undertaken. Key structural differences specific to the CD-associated mRNAs were uncovered, allowing them to strongly interact with TTP through their 3′UTR, conferring a rapid turnover, in contrast to lower affinity binding to HLA non-CD associated mRNA.

HLA class II restriction repertoire of antigen-specific T cells. II. Evidence for a new restriction determinant associated with DRw52 and LB-Q1

1985 ◽  
Vol 13 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Tom H.M. Ottenhoff ◽  
Dienne G. Elferink ◽  
Annemarie Termijtelen ◽  
Frits Koning ◽  
RenéR.P. de Vries
Keyword(s):  
T Cells ◽  
Class Ii ◽  
Hla Class Ii

HLA Class II and class I polymorphism in venezuelan patients with myasthenia gravis

2004 ◽  
Vol 65 (1) ◽  
pp. 54-59 ◽  
Author(s):  
Mercedes T Fernández-Mestre ◽  
Vivian Vargas ◽  
Silvia Montagnani ◽  
Maritza Cotúa ◽  
Violeta Ogando ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Class Ii ◽  
Hla Class Ii ◽  
Class I

scholarly journals Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Paola Cruz-Tapias ◽  
Oscar M. Pérez-Fernández ◽  
Adriana Rojas-Villarraga ◽  
Alberto Rodríguez-Rodríguez ◽  
María-Teresa Arango ◽  
...  
Keyword(s):  
Risk Factor ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Genetic Characteristics ◽  
Latin Americans ◽  
Leukocyte Antigen

The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

scholarly journals HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis.

1996 ◽  
Vol 183 (6) ◽  
pp. 2635-2644 ◽  
Author(s):  
K Ito ◽  
H J Bian ◽  
M Molina ◽  
J Han ◽  
J Magram ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Diseases ◽  
Mhc Class Ii ◽  
Experimental Allergic Encephalomyelitis ◽  
Class Ii ◽  
Antigen Binding ◽  
Allergic Encephalomyelitis ◽  
Alpha Beta ◽  
Deficient Mice ◽  
Experimental Allergic

To investigate the development of HLA-DR-associated autoimmune diseases, we generated transgenic (Tg) mice with HLA-DRA-IE alpha and HLA-DRB1*0401-IE beta chimeric genes. The transgene-encoded proteins consisted of antigen-binding domains from HLA-DRA and HLA-DRB1*0401 molecules and the remaining domains from the IE(d)-alpha and IE(d)-beta chains. The chimeric molecules showed the same antigen-binding specificity as HLA-DRB1*0401 molecules, and were functional in presenting antigens to T cells. The Tg mice were backcrossed to MHC class II-deficient (IA beta-, IE alpha-) mice to eliminate any effect of endogenous MHC class II genes on the development of autoimmune diseases. As expected, IA alpha beta or IE alpha beta molecules were not expressed in Tg mice. Moreover, cell-surface expression of endogenous IE beta associated with HLA-DRA-IE alpha was not detectable in several Tg mouse lines by flow cytometric analysis. The HLA-DRA-IE alpha/HLA-DRB1*0401-IE beta molecules rescued the development of CD4+ T cells in MHC class II-deficient mice, but T cells expressing V beta 5, V beta 11, and V beta 12 were specifically deleted. Tg mice were immunized with peptides, myelin basic protein (MBP) 87-106 and proteolipid protein (PLP) 175-192, that are considered to be immunodominant epitopes in HLA-DR4 individuals. PLP175-192 provoked a strong proliferative response of lymph node T cells from Tg mice, and caused inflammatory lesions in white matter of the CNS and symptoms of experimental allergic encephalomyelitis (EAE). Immunization with MBP87-106 elicited a very weak proliferative T cell response and caused mild EAE. Non-Tg mice immunized with either PLP175-192 or MBP87-106 did not develop EAE. These results demonstrated that a human MHC class II binding site alone can confer susceptibility to an experimentally induced murine autoimmune disease.

scholarly journals Antigen presentation in an HLA-DR-restricted fashion by B-cell chronic lymphocytic leukemia cells

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 102-108 ◽  
Author(s):  
M Yasukawa ◽  
T Shiroguchi ◽  
A Inatsuki ◽  
Y Kobayashi
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Antigen Presentation ◽  
Interleukin 2 ◽  
Class Ii ◽  
Hla Class Ii ◽  
Lymphocytic Leukemia ◽  
Hla Dr ◽  
Cell Chronic Lymphocytic Leukemia

The ability of B-cell chronic lymphocytic leukemia (B-CLL) cells to present antigen to antigen-specific T cells was investigated. B-CLL cells present herpes simplex virus (HSV) antigen and purified protein derivative (PPD) to HSV- and PPD-specific, interleukin-2-dependent T- cell lines in an antigen-specific manner. Treatment of B-CLL cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced markedly increased levels of HLA-DR expression. TPA-treated B-CLL cells showed substantially more effective presentation, especially at low antigen concentrations, than did untreated B-CLL cells. By coculturing different allogeneic combinations of B-CLL cells and T cells and by adding anti-HLA-DR monoclonal antibody to cultures, it was found that antigen presentation by B-CLL cells was restricted by HLA-DR in the same way as for macrophages. We concluded from these experiments that B- CLL cells have a capacity to serve as antigen-presenting cells in an HLA class II-restricted fashion and that increasing the amount of HLA class II antigen and activation of B-CLL cells resulted in effective antigen presentation.

scholarly journals CD4+ T-cell alloreactivity toward mismatched HLA class II alleles early after double umbilical cord blood transplantation

Blood ◽  
2016 ◽  
Vol 128 (17) ◽  
pp. 2165-2174 ◽  
Author(s):  
Cor H. J. Lamers ◽  
Rebecca Wijers ◽  
Cornelis A. M. van Bergen ◽  
Judith A. E. Somers ◽  
Eric Braakman ◽  
...  
Keyword(s):  
T Cells ◽  
Cord Blood Transplantation ◽  
Class Ii ◽  
Hla Class Ii ◽  
Effector T Cells ◽  
Cd4 T Cell ◽  
Blood Transplantation ◽  
Key Points ◽  
Allele Specific ◽  
Hla Class Ii Alleles

Key Points Graft-versus-graft alloreactivity after dUCBT involves recognition of mismatched HLA class II alleles by allele-specific CD4+ effector T cells. Alloreactive donor CD4+ T cells may recognize recipient leukemia if mismatched for individual HLA class II alleles.

scholarly journals Functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ transgenic mice.

1994 ◽  
Vol 180 (1) ◽  
pp. 165-171 ◽  
Author(s):  
K Yamamoto ◽  
Y Fukui ◽  
Y Esaki ◽  
T Inamitsu ◽  
T Sudo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Responses ◽  
Class Ii ◽  
Hla Class Ii ◽  
Functional Interaction ◽  
Leukocyte Antigen ◽  
Cell Responses ◽  
Hla Class Ii Molecules

Studies in vitro have suggested that a species barrier exists in functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecules. However, whether mouse CD4+ T cells restricted by HLA class II molecules are generated in HLA class II transgenic mice and respond to peptide antigens across this barrier has remained unclear. In an analysis of T cell responses to synthetic peptides in mice transgenic for HLA-DR51 and -DQ6, we found that DR51 and DQ6 transgenic mice acquired significant T cell response to influenza hemagglutinin-derived peptide 307-319 (HA 307) and Streptococcus pyogenes M12 protein-derived peptide 347-397 (M6C2), respectively. Inhibition studies with several monoclonal antibodies showed that transgenic HLA class II molecules presented these peptides to mouse CD4+ T cells. Furthermore, T cell lines specific for HA 307 or M6C2 obtained from the transgenic mice could respond to the peptide in the context of relevant HLA class II molecules expressed on mouse L cell transfectants that lack the expression of mouse MHC class II. These findings indicate that interaction between HLA class II and mouse CD4 molecules is sufficient for provoking peptide-specific HLA class II-restricted T cell responses in HLA class II transgenic mice.

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